Nonionic Low-osmolar Contrast Media Research Articles

Omnipaque (iohexol).

The largest nationwide comparative clinical study evaluated 337,647 patients receiving high-osmolar ionic contrast media or low-osmolar nonionic contrast media and the incidence of adverse drug reactions. The overall prevalence of adverse drug reactions was 12.66% in the ionic contrast media group and 3.13% in the nonionic contrast media group. Severe adverse drug reactions occurred in 0.22% of examinations in the ionic contrast media group and in 0.04% of examinations in the nonionic contrast media group. Thus, the use of nonionic contrast medium significantly reduces the frequency of severe and potentially life-threatening adverse drug reactions to contrast media.

Ionized calcium levels in coronary sinus blood during coronary angiography: effects of four contrast media.

The changes in ionized calcium level in the coronary sinus during coronary angiography were compared for four contrast media (meglumine sodium diatrizoate, iohexol, iopamidol, and meglumine sodium ioxaglate) in 44 subjects. Blood samples were collected before and 5, 15, and 30 seconds after injection of contrast medium into the left coronary artery. The hematocrit and ionized calcium level of each specimen were measured. Meglumine sodium diatrizoate produced the largest changes in hematocrit and ionized calcium level. The time-concentration curve of the hematocrit was similar for all four contrast media, but diatrizoate and ioxaglate produced a prolonged decrease of ionized calcium. The cause of this is not clear, but the phenomenon may be related to differences of ionic status among the contrast media. With respect to maintenance of the ionized calcium level, nonionic low-osmolality contrast medium with added calcium may be preferable for coronary angiography.

Decision analysis to assess cost-effectiveness of low-osmolality contrast medium for intravenous urography

Decision analysis was used to compare the cost-effectiveness of a conventional ionic high-osmolality contrast medium with that of a nonionic low-osmolality contrast medium when used for i.v. urography. The patient populations considered in the model were those with a low risk and those with a high risk of contrast medium-associated adverse effects. Mean toxicity rates for the contrast media were obtained from the literature. To estimate the average cost of adverse effects, the probability of a patient in each population developing a mild, moderate, or severe reaction was multiplied by the respective estimated cost for each level of severity, and the products were summed. The incremental cost of the low-osmolality medium per case of adverse effects prevented was calculated by dividing the difference between the average costs of the two media by the difference between the frequencies of toxicity associated with the agents. According to the 1990 cost data used, combined mean drug and toxicity costs were $68 and $13 for the low- and high-osmolality contrast media, respectively, per high-risk patient and $67 and $10 per low-risk patient. The incremental costs of the low-osmolality medium per case of severe adverse effects prevented was $17,974 in the high-risk population and $77,027 in the low-risk population. Sensitivity analysis showed the results to be stable over a range of data used in the model.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of Urography and Renal Clearance of Ionic and Nonionic Contrast Media

The authors evaluated whether urographic quality correlated with patient hydration and the level of their renal function, depending on whether they received ionic or nonionic contrast media. One hundred patients with normal serum creatinine levels were randomly assigned to receive intravenous urography with either an ionic high-osmolar or a nonionic low-osmolar contrast medium. Patient hydration was evaluated by measuring urine osmolality in a sample voided just before the examination. The plasma concentration of iodine was determined in a single blood sample drawn approximately 3 hours later. From these determinations the plasma clearance of contrast medium was calculated. The urograms were assessed blindly with regard to nephrographic and pyelographic opacification, as well as overall diagnostic quality. The clearance varied between 42 and 115 mL x minutes-1 x 1.73 m-2. No systematic correlation of practical significance was found between the clearances and the urogram quality. A high urinary osmolality before the examination tended to improve quality with both media. It is not possible to assess glomerular filtration rate from nephrographic and pyelographic opacification, or from overall quality of routine urograms in patients with normal serum creatinine levels.

Risk of thrombosis during coronary angioplasty with low osmolality contrast media

Studies in vitro have suggested that nonionic low osmolar contrast agents produce an increase in thrombogenicity. To determine the incidence of thrombi related to the use of nonionic low osmolar contrast media during coronary angioplasty, a double-blind randomized study was performed in 100 patients. Medication before angioplasty included oral aspirin (250 mg/day) in all cases. At the beginning of the procedure, aspirin (250 mg) and heparin (10,000 U) were intravenously administered. During the procedure patients were randomly assigned to receive either an ionic low osmolar contrast agent ioxaglate (n = 50), or a nonionic low osmolar contrast media iohexol (n = 50). The presence of thrombus was evaluated on the angiogram and on the guidewire immediately after its retrieval from the patients. Clinical, angiographic and procedural variables were similar in the 2 randomized groups. Angiographic evidence of thrombus was observed in 1 patient (2%) assigned to ioxaglate and in 11 patients (22%) assigned to iohexol (p < 0.005). One patient (2%) from the ioxaglate group and 6 patients (12%) from the iohexol group showed thrombotic residues on the guidewire (p = not significant). Three patients had acute myocardial infarction, 1 patient (2%) receiving ioxaglate and 2 patients (4%) iohexol (p = not significant). There were no deaths. Thus, compared with an ionic low osmolar contrast media ioxaglate, the nonionic low osmolar contrast agent iohexol increases the incidence of thrombus during coronary angioplasty.

Renal Clearance of an Ionic High-Osmolar and a Nonionic Low-Osmolar Contrast Medium

One hundred patients with normal serum creatinine concentration underwent intravenous urography with either an ionic high-osmolar (diatrizoate) or a nonionic low-osmolar (iopamidol) contrast medium after randomization. Before injection of the contrast medium, a blood sample was drawn for determinating serum creatinine concentration, and a urine sample for measurement of urine osmolality. Using x-ray fluorescence, the plasma concentration of iodine (contrast medium) was determined on blood samples drawn approximately 3 and 4 hours after injection of the contrast medium. The glomerular filtration rate was calculated by two different formulas: one requiring only a single sample and one requiring at least two samples (standard). There were poor correlations between the standard contrast medium clearance and the serum creatinine concentration, the estimated creatinine clearance (calculated from a nomogram), as well as the urine osmolality. The 3-hour and the 4-hour single-sample values correlated well with the two-sample values for both contrast media. In patients with normal serum creatinine, the glomerular filtration rate determined by measuring the contrast medium concentration in a single plasma sample obtained at 3 hours, is almost identical to the value determined from two samples. Consequently, two samples are unnecessary.

Miscellaneous adverse effects of low-versus high-osmolality contrast media: a study revised.

The authors analyzed data from two recent articles in Radiology in which the quality and results of randomized control trials (RCTs) comparing the efficacy or safety of the low-osmolality contrast media (LOM) iopamidol, iohexol, and ioxaglate with that of the high-osmolarity contrast media (HOM) diatrizoate, iodamide, iopamide, iothalamate, and metrizoate were assessed. One conclusion in the source articles was that no differences were seen between the two groups of contrast media in frequency of nausea, vomiting, and urticaria. However, the LOM group included both nonionic LOM (NIM) and the ionic contrast medium ioxaglate. The authors found that various complications associated with the use of contrast media were much less common with NIM than with HOM; statistically this lower frequency is highly significant. This difference was obscured in the previous studies by the pooling of RCTs in which the less toxic NIM were used and RCTs in which the more toxic ionic contrast medium ioxaglate was used.

Prediction of severe adverse reactions to ionic and nonionic contrast media in Japan: evaluation of pretesting. A report from the Japanese Committee on the Safety of Contrast Media.

In a nationwide prospective study of adverse reactions to intravenous contrast media (CM), the Japanese Committee on the Safety of Contrast Media compared high-osmolar ionic CM with low-osmolar nonionic CM. A total of 337,647 cases were analyzed. The reliability of pretesting with an intravenous injection of a small amount of CM as a means of predicting severe or fatal reactions was also evaluated. The predictive values of the pretest were 1.2% for ionic and 0.0% for nonionic CM, and the sensitivity values were 3.7% and 0.0%, respectively. Such low values render this test meaningless for predicting which patients are at risk of a severe adverse reaction. A comparison of the incidence of severe adverse reactions between the nonpretested and pretested patients, as well as between the nonpretested and pretested patients with negative results, disclosed no statistically significant differences. Also, no beneficial effects of premedication in patients with a positive pretest were proved. The authors therefore conclude that pretesting with an intravenous injection of a small amount of CM is not useful in predicting severe reactions to ionic or nonionic CM.

Variable Effects of Radiological Contrast Media on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

We studied the effect of an ionic high osmolar contrast medium (Ioxitalamate), an ionic low osmolar contrast medium (Ioxaglate) and various nonionic low osmolar contrast media (Iopamidol, Iopromide and Iohexol) on thrombus growth in a rabbit jugular vein thrombosis model. Thrombus growth was determined by the accretion of 125I-labeled fibrinogen onto autologous preformed thrombi in rabbit jugular veins at various time-intervals from 15 min up to 10 h after infusion of the study solution. The ionic low osmolar contrast medium markedly inhibited thrombus growth whereas all nonionic low osmolar contrast media promoted thrombus growth. The ionic high osmolar, contrast medium inhibited thrombus growth, but less than the ionic low osmolar contrast medium. Within the group of nonionic contrast media, the Iopamidol associated promotion of thrombus growth was significantly higher than the Iopromide or Iohexol associated effects. The simultaneous administration of the apparently most potent thrombus growth promoting contrast medium (i.e. Iopamidol) and heparin resulted in complete abolishment of the increase in thrombus growth. These results support the claims of prothrombotic properties of nonionic as compared to ionic contrast media and could explain the clinically encountered thromboembolic complications after the use of nonionic low osmolar contrast media.

Perspectives on Adverse Reaction Rates Associated with the Use of High Osmolar Ionic and Low Osmolar Nonionic Contrast Media

This report considers the toxicological evidence from conventional whole animal and special in vitro toxicological studies and the results of clinical studies of adverse reaction rates in humans, using the methods of epidemiology

Are ioxaglate and iopamidol equally safe and well tolerated in cardiac angiography? A randomized, double-blind clinical study

A randomized, double-blind, parallel-group study was performed in 50 patients undergoing left ventriculography and coronary arteriography to evaluate ECG changes and the effects on left ventricular function of a low-osmolar lonic contrast agent, ioxaglate, as compared with a low-osmolar nonionic contrast medium, iopamidol. Twenty-five patients received ioxaglate (group 1) and 25 patients received iopamidol (group 2). All patients underwent 48 hours of continuous ECG recording beginning 24 hours before the cardiac catheterization. Left ventricular systolic and end-diastolic pressure, peak positive dp dt , and dp/dt/P ratio were measured immediately before and after left ventriculography and 3 minutes later. Left ventricular systolic pressure did not change after injection of either contrast medium. Left ventricular and-diastolic pressure increased by 30% in group 1 ( p < 0.01) and by 22% in group 2 ( p < 0.01) immediately after left ventriculography. A further increase by 45% in group 1 ( p < 0.01) and by 24% in group 2 ( p < 0.01) was observed 3 minutes later. No differences were observed between values obtained in the two groups. Peak positive dp dt did not change immediately after injection of either contrast medium but decreased by 5% (not significant) in group 1 and by 7% ( p < 0.02) in group 2 three minutes after left ventriculography. There were no significant differences between the two groups. Analysis of continuous 48-hour ECGs showed that both ioxaglate and iopamidol induced a slight increase (by 8% and 7%, respectively; p < 0.05) in heart rate during injection with early and complete recovery. A significant increase in the frequency of ventricular premature complexes (total number/1000/hr) was observed in group 2 during the injection period and during the first hour after completion of contrast injection with respect to the extreme intervals ( p < 0.05). Furthermore, bigeminal rhythm, pairs, and R-on-T ventricular premature complexes increased by 24% in group 1 and by 636% in group 2 ( p < 0.02) during injection. PR interval, QRS width, corrected QT interval and ST segment did not change throughout the study. Thus results of our study show that despite simillar effects of ioxaglate and iopamidol on left ventricular function, the occurrence of potentially harmful ventricular arrhythmias is more frequent with iopamidol.

Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media.

A large-scale (337,647 cases), nationwide comparative clinical study in Japan on adverse drug reactions (ADRs) to high-osmolar ionic contrast media and low-osmolar nonionic contrast media was performed prospectively. Ionic contrast media were administered in 169,284 cases (50.1%) and nonionic contrast media in 168,363 cases (49.9%). The overall prevalence of ADRs was 12.66% in the ionic contrast media group and 3.13% in the nonionic contrast media group. Severe ADRs occurred in 0.22% of the ionic and 0.04% of the nonionic contrast media examinations. One death occurred in each group, but a causal relationship to the contrast medium could not be established. It is concluded that nonionic contrast media significantly reduce the frequency of severe and potentially life-threatening ADRs to contrast media at all levels of risk and that use of these media represents the most effective means of increasing the safety of contrast media examinations.

Effect on Thrombus Growth and Thrombolysis of Two Types of Low Osmolar Contrast Media in Rabbits

Thromboembolic complications have been reported after diagnostic or interventional radiological procedures. However, contrast media inhibit platelet function and blood coagulation in vitro. To investigate these characteristics in vivo, we determined the effect of nonionic and ionic low osmolar contrast media on thrombus growth and thrombolysis in rabbits in a randomized study design. Rabbits received either ionic low osmolar contrast medium (ioxaglate), nonionic low osmolar contrast medium (iohexol) or saline. Thrombus growth was determined by the accretion of 125I-labeled fibrinogen on to autologous, nonradioactive, preformed thrombi in rabbit jugular veins. Thrombolysis was assessed by measurement of the decrease in radioactivity of standard sized preformed 125I-fibrinogen labeled thrombi. Ioxaglate significantly inhibited thrombus growth (60% inhibition, P less than 0.005 vs. saline), in contrast to iohexol, which had no significant effect (33% inhibition, P less than 0.2 vs. saline). Neither ioxaglate nor iohexol affected thrombolysis.

Ventricular fibrillation during coronary angiography: Reduced incidence with nonionic contrast media

Ventricular fibrillation during coronary angiography with Renografin-76 has been attributed to the high osmolar ionic and calcium binding additive properties. Isovue-370 is a new low osmolar nonionic contrast medium lacking calcium binding additives. The present investigation compared the incidence of contrast media-induced ventricular fibrillation in patients undergoing coronary angiography with Renografin-76 to that with Isovue-370. Group I consisted of 2,000 consecutive patients undergoing coronary angiography with Renografin-76, and group II consisted of 2,000 subsequent consecutive patients in whom Isovue-370 was employed as the contrast medium. There was no significant difference between groups I and II with respect to volume of contrast media used per patient (125 +/- 35 vs. 140 +/- 45 ml), age (63.5 +/- 15 vs. 60 +/- 17 years), sex (74% male vs. 76% male), ejection fraction (55% vs. 55%), valvular heart disease (8% vs. 9%), prior coronary artery bypass graft surgery (5.8% vs. 5%), or extent of coronary artery disease. Contrast media-induced ventricular fibrillation occurred in 20 patients in group I (incidence 1%), whereas eight episodes occurred in group II (incidence 0.4%) (P less than 0.03). Thus the present investigation suggests that the incidence of ventricular fibrillation during coronary angiography can be significantly decreased by using low osmolar nonionic contrast media lacking calcium binding additives.

Elimination of lohexol, a Low Osmolar Nonionic Contrast Medium, by Hemodialysis in Patients with Chronic Renal Failure

The dialyzability of iohexol was examined in patients with chronic renal failure on long-term hemodialysis treatment. Eight patients had iohexol (Omnipaque 240 or 350 mg I/ml) injected in doses between 98 and 1,493 mg I/kg body weight (BW) 25 h (mean time) before start of hemodialysis. Dialysance of iohexol was 81 +/- 15 ml/min (mean +/- SD) compared to 120 +/- 16.8 ml/min for creatinine. Elimination half-life for iohexol during hemodialysis was 3.9 +/- 1.1 h while plasma clearance was 64 +/- 17 ml/min. The distribution volume calculated (0.25 +/- 0.05 liters/kg BW) confirms previous observations with distribution in the extracellular fluid only. Before the start of hemodialysis 36 +/- 28% of the dose injected was eliminated, indicating some extrarenal elimination. After 4 h of hemodialysis 72 +/- 11% of the dose was removed.

Adriamycin Nephrosis and Contrast Media

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 9 days after intravenous injection of either diatrizoate, iohexol, or saline in 27 Wistar rats with nephrosis induced by Adriamycin 42 days before. Another 9 rats exposed to neither Adriamycin nor contrast media served as controls. None of the contrast media caused further increased albuminuria of significance, whereas both induced significantly increased excretion of all 5 tubular components. The excretion of NAG and sodium was significantly higher following diatrizoate than following iohexol. From 24 h post injection there was no significantly greater excretion of any of the components after either diatrizoate or iohexol than after saline among the rats given Adriamycin. At the end of day 9 after contrast medium injection neither serum sodium, potassium, glucose, urea, creatinine, nor albumin revealed any contrast media related changes. Kidney histology showed quantitatively larger lesions in kidneys exposed to Adriamycin and contrast media than in kidneys exposed to Adriamycin and saline. There were no differences between the two contrast media groups. It is thus concluded, that both high osmolar ionic and low osmolar non-ionic contrast media cause temporary tubular dysfunction but no further glomerular dysfunction in rats with nephrosis induced by Adriamycin. The histologic findings indicate that both media may worsen non-reversible renal lesions.

Effects on Renal Hemodynamics and Tubular Function of the Contrast Medium Iohexol in Renal Patients

Renal function was assessed in 20 (11 female and 9 male, age 21-76 years, mean 53) renal patients with a creatinine clearance 25-145 ml/min, mean 95, to evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium. Intravenous urography was performed in 16 patients and computed body tomography in 4, using a dose of iohexol ranged between 0.6-3.3 (mean 1.17) g/kg b.w. Different parameters of renal function were determined in the week preceding and 1, 3 and 5 days after the administration of iohexol. The principal renal effect of iohexol was an increase of urinary alanine aminopeptidase, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase. The maximum increase of enzymuria was observed on day 1 after the administration of iohexol. In most cases enzymes returned to base-line values within 3 days. No relevant variation of renal hemodynamics (glomerular filtration rate and effective renal plasma flow) was observed after iohexol. In conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly reversible and is not accompanied by a clinically significant impairment of renal hemodynamics.

The reaction of cerebral arteries to non-ionic contrast media during cerebral angiography.

The purpose of this study was to evaluate possible vasoconstrictive or vasodilatator effects of the low osmolar non-ionic contrast medium iohexol (Omnipaque) on the calibre of cerebral arteries. The diameters of respectively 5 and 6 different locations of the vertebral and carotid arteries were recorded from angiograms of 3 successive injections. The material consisted of 18 patients. It could not be shown that Omnipaque induced vasoconstriction or vasodilatation when normal doses and adequate technique was applied. The difference in diameters found were not statistically significant and are probably due to natural pulsations and to the difficulties in performing exact measurements.

Safety of the nonionic contrast medium omnipaque in coronary angiography

The low osmolar nonionic contrast medium Omnipaque was used in 5,339 consecutive coronary angiographies and serious complications were registered. Myocardial infarction occurred in 4 patients, of whom 2 died, and ventricular fibrillation in 1. Cerebral embolism occurred in 11 patients, all of whom survived. The results are compared with those of previous series of coronary angiography with high osmolar ionic media. It is concluded that use of the nonionic medium Omnipaque resulted in a significant reduction of the frequency of serious complications.

Nephropathy Induced by Intramuscularly Administered Glycerol and Contrast Media in Rats

Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy.